Research, Research Articles
Transcriptomic response to different heme sources in Trypanosoma cruzi epimastigotes
Evelyn Tevere1,a, María G. Mediavilla1,a, Cecilia B. Di Capua1, Marcelo L. Merli1, Carlos Robello2,3, Luisa Berná2,4 and Julia A. Cricco
This study uncovers how the Chagas disease parasite adapts to changes in heme, an essential molecule for its survival, providing transcriptional clues to heme metabolism and identifying a previously unreported heme-binding protein in T. cruzi.
Sir2 regulates selective autophagy in stationary-phase yeast cells
Ji-In Ryua, Juhye Junga, and Jeong-Yoon Kim
This study establishes Sir2 as a previously unrecognized regulator of selective autophagy during the stationary phase and highlight how cells dynamically control organelle degradation.
Luminal acetylation of microtubules is not essential for Plasmodium berghei and Toxoplasma gondii survival
Thrishla Kumar1,a, Katharina Röver2,a, Johannes F. Stortz3,a, Annika M. Binder2,a, Benjamin Spreng2, Madlen Konert2, Markus Meissner1, Friedrich Frischknecht2,4 and Elena Jimenez-Ruiz1,*
Acetylation of α-tubulin at lysine 40 is not essential for cytoskeletal stability in Plasmodium berghei or Toxoplasma gondii, suggesting redundancy and plasticity in microtubule regulation in these parasites.
The dual-site agonist for human M2 muscarinic receptors Iper-8-naphtalimide induces mitochondrial dysfunction in Saccharomyces cerevisiae
Angela Cirigliano1,a, Antonia Amelina2,a, Elena Passarini2, Alessandra Ricelli1, Nicole Balasco1, Mattia Mori3, Bruno Botta4, Maria Egle De Stefano2,5, Claudio Papotto6, Claudia Guerriero2, Ada Maria Tata2,5 and Teresa Rinaldi2,*
S. cerevisiae is a model to study human GPCRs. N-8-Iper, active against glioblastoma via M2 receptor, causes mitochondrial damage in yeast by binding Ste2, highlighting evolutionary conservation of GPCRs.
The core genetic drivers of chronological aging in yeast are universal regulators of longevity
Erika Cruz-Bonilla1, Sergio E. Campos2, Soledad Funes3, Cei Abreu-Goodger4 and Alexander DeLuna1,2,*
This study provides an integrated view of the core genetic landscape underlying aging in yeast, highlighting the value of the chronological lifespan paradigm for investigating conserved mechanisms of aging.
Organelle activity organized by the endoplasmic reticulum-mitochondria encounter structure –ERMES– is essential for Podospora anserina development
Melisa Álvarez-Sánchez1, Matías Ramírez-Noguez1, Beatriz Aguirre-López1 and Leonardo Peraza-Reyes1
This study shows that the regulation of the activity of multiple organelles by the ERMES (Endoplasmic Reticulum-Mitochondria Encounter Structure) tethering complex is essential for fungal growth and sexual development.
Role of the putative sit1 gene in normal germination of spores and virulence of the Mucor lusitanicus
Bernadett Vágó1,2, Kitti Bauer1,2, Naomi Varghese1,2, Sándor Kiss-Vetráb1,2, Sándor Kocsubé1,2, Mónika Varga1,2, András Szekeres1,2, Csaba Vágvölgyi1,2, Tamás Papp1,2,3,# and Gábor Nagy1,2,3,#
Mucormycosis is a life-threatening infection caused by certain members of the fungal order Mucorales, with increased incidence in recent years. Individuals with untreated diabetes mellitus, and patients treated with deferoxamine are particularly susceptible to this infection.
Tumor microenvironment signatures enhances lung adenocarcinoma prognosis prediction: Implication of intratumoral microbiota
Fei Zhao1,#, Lei Wang2,3,4,#, Dongjie Du5, Heaven Zhao6,7, Geng Tian6,7, Yufeng Li2,3,8, Yankun Liu2,8,9, Zhiwu Wang2,3,10, Dasheng Liu11, Jingwu Li2,3,12, Lei Ji6,7 and Hong Zhao1
The interaction between intratumoral microbiome and the tumor microenvironment (TME) has furthered our understanding of tumor ecology. Yet, the implications of their interaction for lung cancer management remain unclear.
Persistence phenotype of adherent-invasive Escherichia coli in response to ciprofloxacin, revealing high-persistence strains
Valeria Pérez-Villalobos1, Roberto Vidal2, Marcela A. Hermoso3,4 and Paula Bustamante1
We investigated the roles of the resident antibiotic resistance plasmid, the stress response protein HtrA, and macrophage-induced persister formation. Our results revealed broad variability in persister cell formation among AIEC strains.
Impact of histone H4K16 acetylation on the meiotic recombination checkpoint in Saccharomyces cerevisiae
December 4, 2016
In meiotic cells, the pachytene checkpoint or meiotic recombination checkpoint is a surveillance mechanism that monitors critical processes, such as recombination and chromosome synapsis, which are essential for proper distribution of chromosomes to the meiotic progeny. We report here that Sas2-mediated acetylation of histone H4 at lysine 16 (H4K16ac) modulates meiotic checkpoint activity in response to synaptonemal complex defects. Our results reveal that proper levels of H4K16ac orchestrate this meiotic quality control mechanism and that Sir2 impinges on additional targets to fully activate the checkpoint.
The transcription factors ADR1 or CAT8 are required for RTG pathway activation and evasion from yeast acetic acid-induced programmed cell death in raffinose
December 2, 2016
Yeast Saccharomyces cerevisiae grown on glucose undergoes programmed cell death (PCD) induced by acetic acid (AA-PCD), but evades PCD when grown in raffinose. This is due to concomitant relief of carbon catabolite repression (CCR) and activation of mitochondrial retrograde signaling. In this work, we investigated the relationships between the RTG and CCR pathways in the modulation of AA-PCD sensitivity under glucose repression or de-repression conditions. Our data show that simultaneous mitochondrial retrograde pathway activation and SNF1-dependent relief of CCR have a key role in central carbon metabolism reprogramming which modulates the yeast acetic acid-stress response.
The ubiquitin-conjugating enzyme, Ubc1, indirectly regulates SNF1 kinase activity via Forkhead-dependent transcription
November 5, 2016
The SNF1 kinase class of serine/threonine kinases, which includes the AMP-dependent protein kinase (AMPK) in other systems, are of widespread interest because of their important roles in glucose homeostasis, stress resistance, and aging. Our goal was to identify discrete ubiquitin-conjugating enzymes that are involved in SNF1 kinase activity in response to glucose levels and anticipated revealing those which are involved in Snf1-Ub attachment. Here, we report that the cell cycle and stress-related E2, Ubc1, indirectly affects SNF1 kinase activity not through stability, but through upstream events.
Phylogenetic profiles of all membrane transport proteins of the malaria parasite highlight new drug targets
August 30, 2016
In order to combat the on-going malaria epidemic, discovery of new drug targets remains vital. Proteins that are essential to survival and specific to malaria parasites are key candidates. Here, we present a comprehensive orthology assignment of all Plasmodium falciparum putative membrane transport proteins and provide a detailed overview of the associated essential gene functions obtained through experimental genetics studies in human and murine model parasites.
VDAC regulates AAC-mediated apoptosis and cytochrome c release in yeast
August 25, 2016
Mitochondrial outer membrane permeabilization is a key event in apoptosis processes leading to the release of lethal factors. In this study, we sought to determine whether Por1p functionally interacts with ADP/ATP carrier (AAC) proteins, as well as its contribution to cytochrome c release and yeast apoptosis induced by acetic acid treatment. Our data indicate that Por1p may regulate cell survival by acting as a negative regulator of AAC proteins in the apoptotic cascade.
Attenuation of polyglutamine-induced toxicity by enhancement of mitochondrial OXPHOS in yeast and fly models of aging
July 26, 2016
Defects in mitochondrial biogenesis and function are common in many neurodegenerative disorders, including Huntington’s disease (HD). We could shown that enhancement of mitochondrial biogenesis protects against neurodegeneration in HD yeast and fly models. Our results suggest that therapeutic interventions aiming at the enhancement of mitochondrial respiration and OXPHOS could reduce polyQ toxicity and delay disease onset.
Cox1 mutation abrogates need for Cox23 in cytochrome c oxidase biogenesis
June 30, 2016
Cox23 is a known conserved assembly factor for cytochrome c oxidase, although its role in cytochrome c oxidase (CcO) biogenesis remains unresolved. To gain additional insights into its role, we isolated spontaneous suppressors of the respiratory growth defect in cox23∆ yeast cells. In this report, we describe the isolation of a robust suppressor of the respiratory defect in cox23∆ cells that mapped to the mitochondrial-encoded Cox1 subunit.
Increased spontaneous recombination in RNase H2-deficient cells arises from multiple contiguous rNMPs and not from single rNMP residues incorporated by DNA polymerase epsilon
May 15, 2016
Ribonucleotides (rNMPs) can become embedded in DNA from insertion by DNA polymerases, failure to remove Okazaki fragment primers, R-loops that can prime replication, and RNA/cDNA-mediated recombination. We report here that recombination is not stimulated by rNMPs incorporated by the replicative polymerase epsilon. Instead, recombination seems to be stimulated by multiple contiguous rNMPs, which may arise from R-loops or replication priming events.
Construction and evaluation of yeast expression networks by database-guided predictions
May 10, 2016
DNA-Microarrays are powerful tools to obtain expression data on the genome-wide scale. We set out to define a way to cluster microarray data according to their expressional relationship and to obtain information on the significance of this clustering approach.
Optogenetic monitoring identifies phosphatidylthreonine-regulated calcium homeostasis in Toxoplasma gondii
May 1, 2016
Toxoplasma gondii is an obligate intracellular parasite, which inflicts acute as well as chronic infections in a wide range of warm-blooded vertebrates. Using an optogenetic sensor to monitor subcellular calcium in this model intracellular pathogen we found a novel regulatory function of phosphatidylthreonine in calcium signaling.